Behavioral deficits of alcoholics have been conceptualized in terms of two neuropathologically distinct syndromes: alcoholic dementia and Korsakoff's psychosis (alcohol amnestic disorder). Alcoholic dementia is characterized by diffuse cortical damage primarily related to the neurotoxicity of alcohol; Korsakoff's psychosis has subcortical lesions due to nutritional (thiamine) deficits. Severe and persistent memory impairment with relative sparing of other intellectual functions distinguishes Korsakoff's psychosis from alcoholic dementia which may not be distinguishable from Alzheimer's disease on cross-sectional clinical evaluation. We have found that Korsakoff patients have reduced REM latencies compared to normal volunteers whereas those with Alzheimer's disease have normal REM latencies. Furthermore, delta sleep which is reduced in Alzheimer's disease is normal in Korsakoff patients. Genetic differences in thiamine metabolism may predispose patients to develop Korsakoff's psychosis. All of the three patients with Korsakoff's psychosis we have studied to date have a transketolase with reduced affinity for thiamine pyrophosphate. The majority of alcoholics have aspects of both syndromes. Since pharmacologic modulation of neurotransmitter systems may be effective in treatment of the subcortical syndrome, this protocol is intended to utilize clinical, neuroradiological, physiological and neuropharmacological tests to differentiate these two pathologic entities, to follow longitudinal course and to relate variables in treatment protocols to outcome.